Chemistry analyzers occupy a preeminent position in the clinical environment, providing significant data regarding the diagnosis and treatment of patient illnesses. Accordingly, there has been a concerted effort by many investigators to develop automated and manual methods for the determination and qualification of constituents in body fluids such as acid phosphatase, alanine aminotransferase, albumin, aldolase, alkaline phosphatase, alpha-hydroxybutyrate dehydrogenase, amylase, aspartate aminotransferase, bicarbonate, direct bilirubin, total bilirubin, blood urea nitrogen, total calcium, carbon dioxide, chloride, total cholesterol, cholinesterase, cortisol, creatine kinase, creatine, digoxin, gamma glutamyl-transferase, globlin, glucose, ldh-cholesterol, iron, lactate dehydrogenase-1, lactate, osmolality, phenylalanine, phosphorus, potassium, salicylate, sodium, T3, T3 uptake, T4, total iron binding capacity, tri glycerides, and uric acid.
Both the manual and automated methods available for each one of the above analytes require either controls or reagents whereby the procedures and other variable parameters of the clinical chemistry analyzers may be checked to ensure accuracy of the testing method or instrument.
Conventional attempts to prolong the stability of chemistry controls and related reagents include reduction of the controls to a dry format which is typically refrigerated at approximately 4.degree. C. Often, the dry format is made by lyophilization rather than spray drying as the former operates at far lower temperatures than the latter. Heat aggravates degradation of analytes and proteins in general and thus, cold processes such as freeze concentration and freeze drying, have been preferred. Although stability in a lyophilized state is enhanced over that associated with the aqueous format, significant losses in constituent activity levels of known chemistry controls are incurred.
One attempt at a freeze-stable liquid blood control standard is disclosed in U.S. Pat. No. 4,199,471 to A. L. Louderback, et al. The standard comprises a sealed receptacle containing specifically treated red cells and a gaseous head space at least equal to about the volume of the red cells. The special treatment comprises thoroughly washing and separating the red cells from the plasma components and mild treatment with aldehyde, slow admixture and lower aliphatic diol or triol, and retention in a buffered solution. The special treatment optionally includes treating at least a portion of the red cells with carbon monoxide. The head space comprises from 0-15% CO.sub.2, 0-25% O.sub.2 and the balance N.sub.2 and/or inert gas.
A different approach to stabilizing liquid clinical controls is disclosed in U.S. Pat. No. 4,121,905 to Jonas Maurukus. Biological reference materials are lyophilized rapidly at -20.degree. to -30.degree. C., then reconstituted in a medium having 20-50% by weight of an alkylene polyol. The claimed stability is 4 to 5 weeks at 2.degree. to 8.degree. C.